Continuous acidification demineralization process for producing osteoinductive bone; and osteoinductive bone produced thereby

Abstract

The invention is directed to a process for producing demineralized osteoinductive bone, and demineralized osteoinductive bone produced thereby. The process achieves demineralization of bone by subjecting bone, including for example ground bone, bone cubes, chips, strips, or essentially intact bone, to a rapid continuous acid demineralization process. The process includes subjecting bone to a continuous exchange of demineralizing acid solution where the demineralizing acid solution is recirculated from the substantially closed container through an ion exchange media to remove calcium and phosphate thereby producing a regenerated acid, and returning the regenerated acid to the substantially closed container to produce osteoinductive demineralized bone. The process allows bone to be rapidly demineralized to a precise and specific desired residual calcium level, without sacrificing osteoinductivity.

Description

FIELD OF THE INVENTION [0001] The invention is a process for producing demineralized osteoinductive bone, and demineralized osteoinductive bone produced thereby. The process achieves demineralization of bone by subjecting bone, including for example ground bone, bone cubes or strips, and essentially intact bone; to a continuous exchange of acid. The process allows bone to be rapidly demineralized to a precise and specific desired residual calcium level, without sacrificing osteoinductivity. BACKGROUND OF THE INVENTION [0002] Demineralized freeze-dried bone allograft is widely used in the repair of skeletal defects and periodontal disease. It is known that the implantation of acid demineralized bone in the form of a powder in extraskeletal sites may stimulate new bone formation. Various groups including Syftestad, 1982; Urist et al., 1967; Urist and Strates, 1979; Urist and Strates, 1971; Urist et al., 1983; have suggested that a noncollagenous protein or proteins present in deminera...

AI Technical Summary

Benefits of technology

[0004] The invention achieves high demineralization rates by subjecting bone, for example ground cortical bone, to rapid and continuous exchanges of acid. Suitable acids include both highly ionized and / or weak acids. The inventors have discovered that the acid neutralization rate of bone mineral apatite is highly dependent upon the bone surface concentration of the acid and the demineralization reaction products. The initial reaction rate of the acid at the surface of the bone particle is very rapid and quickly terminates, due to boundary layer resistance caused by the increasing concentrations of the reaction by-products, if the residual reaction products are not promptly removed. Since the bone is subjected to the demineralizing acid for very brief periods of time, bone-inducing proteins are not adversely affected, thus resulting in a bone product, which achieves maximum potential osteoinductivity. The process also allows the demineralization of an entire single donor's tissue volume in a single batch.

[0006] The invention also provides a rapid demineralization process for producing osteoinductive bone, including subjecting bone to a continuous exchange of a predetermined volume of one or more demineralizing acid solutions under conditions effective to produce demineralized bone.

Problems solved by technology

These known methods are problematic in that they require prohibitively long periods of time for processing resulting in a very low demineralization rate; require excessive handling of the ground bone being processed; are capable of processing only small amounts of ground bone; and result in a demineralized bone product which exhibits inferior osteoinductivitiy caused by excessive exposure of bone inducing proteins in the bone to harsh acids over extended periods of time.

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